Hemodynamic and Echocardiographic Assessment of Riociguat Effects on Myocardial Wall Contractility and Relaxation Kinetics (HEARTWORK)

A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Effects of a Single Dose of 1 mg Riociguat (BAY63-2521) on Myocardial Contractility and Relaxation in Patients With Pulmonary Hypertension Associated With Left Ventricular Systolic Dysfunction (PH-sLVD)

The aim of this study is to assess whether oral Riociguat affects the left ventricular contractility and relaxation in patients with pulmonary hypertension associated with left ventricular systolic dysfunction

Study Overview

• Status: Terminated
• Conditions: Hypertension, Pulmonary; Ventricular Dysfunction, Left
• Intervention / Treatment: Drug: Placebo; Drug: Riociguat (Adempas, BAY63-2521)

Detailed Description

Adverse event data will be covered in Adverse events section.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
  • Minnesota
    • Rochester, Minnesota, United States, 55905

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients with symptomatic pulmonary hypertension due to left ventricular systolic dysfunction despite standard heart failure therapy

Exclusion Criteria:

• Types of pulmonary hypertension other than group 2.1 of Dana Point Classification

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Riociguat (Adempas, BAY63-2521); Participants received a single oral dose of 1 mg riociguat.	Drug: Riociguat (Adempas, BAY63-2521); 1 mg single oral dose
Placebo Comparator: Placebo; Participants received a single oral dose of 1 mg placebo.	Drug: Placebo; Single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Power Index at Rest	The peak power index is a calculated hemodynamic parameter. It is derived from the directly measured parameters mean systolic arterial pressure (SAPmean) and mean pulmonary capillary wedge pressure (PCWPmean). These 2 parameters are acquired during a right heart catheterization. The peak power index is calculated from the maximal power (which also takes the calculated parameter cardiac output into account) divided by the left ventricular end-diastolic volume (LVEDV). Formula: Peak Power Index = (SAPmean - PCWPmean)*CO [cardiac output]*16.667/LVEDV	Before and 1 hour after administration of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left Ventricular Stroke Work Index (LVSWI) at Rest	The left ventricular stroke work index (LVSWI) is a calculated hemodynamic parameter. It is derived from the directly measured parameters mean systolic arterial pressure (SAPmean) and mean pulmonary capillary wedge pressure (PCWPmean). These 2 parameters are acquired during a right heart catheterization. The LVSWI is also dependent of the calculated hemodynamic parameter stroke volume index (SVI). Formula: LVSWI = (SAPmean - PCWPmean)*SVI*0.0136	Before and 1 hour after administration of study drug
Change in Left Ventricular Ejection Fraction (LVEF) at Rest	The left ventricular ejection fraction work index (LVEF) is a calculated echocardiography parameter. LVEF is derived from the directly measured parameters left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). These 2 parameters are acquired during a non-invasive echocardiography examination. Formula: LEVF = 100*(LVEDV - LVESV)/LVEDV	Before and 1 hour after administration of study drug
Change in End-systolic Elastance at Rest	The end-systolic elastance is a calculated hemodynamic parameter. It is approximated by the directly measured hemodynamic parameter end-systolic pressure divided by the directly measured echocardiography parameter left ventricular end-systolic volume (LVESV). The end-systolic pressure is acquired during a right heart catheterization. The LVESV is acquired during a non-invasive echocardiography examination. Approximated by end-systolic pressure/LVESV	Before and 1 hour after administration of study drug
Change in Peak Power Index During the Cardiopulmonary Exercise Tests	The peak power index is a calculated hemodynamic parameter. It is derived from the directly measured parameters mean systolic arterial pressure (SAPmean) and mean pulmonary capillary wedge pressure (PCWPmean). These 2 parameters are acquired during a right heart catheterization. Formula: Peak Power Index = (SAPmean - PCWPmean)*CO*16.667/LVEDV	Before and 1 hour after administration of study drug
Change in Lateral Mitral Annular Peak Systolic Velocity (Sm) During the Cardiopulmonary Exercise Tests	The lateral mitral annular peak systolic velocity (Sm) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.	Before and 1 hour after administration of study drug
Change in Peak Systolic Tricuspid Annular Velocity (RV-Sm) During the Cardiopulmonary Exercise Tests	The peak systolic tricuspid annular velocity (RV-Sm) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.	Before and 1 hour after administration of study drug
Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) During the Cardiopulmonary Exercise Tests	The tricuspid annular plane systolic excursion (TAPSE) is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.	Before and 1 hour after administration of study drug
Change in Lateral Mitral Annular Peak Early Diastolic Velocity (E') During the Cardiopulmonary Exercise Tests	The lateral mitral annular peak early diastolic velocity (E') is a measured echocardiography parameter. It is acquired during a non-invasive echocardiography examination.	Before and 1 hour after administration of study drug
Change in the Slope of the Relationship Between Work Rate and Mean Pulmonary Arterial Pressure (PAPmean) During the Cardiopulmonary Exercise Tests	The slope of the relationship between work rate during cardiopulmonary exercise tests and PAPmean is derived from the directly measured hemodynamic parameter mean pulmonary arterial pressure (PAPmean). PAPmean is acquired during a right heart catheterization.	Before and 1 hour after administration of study drug
Change in the Ventilatory Efficiency (V'E/V'CO2) Measured From Baseline to the Anaerobic Threshold (AT) During the Cardiopulmonary Exercise Tests (CPET)	Ventilatory efficiency (V'E/V'CO2) and anaerobic threshold (AT) were parameters directly measured or derived by computed analysis from the spiroergometry system during the cardiopulmonary exercise test.	Before and 1 hour after administration of study drug

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 8, 2010
• First Submitted That Met QC Criteria: February 8, 2010
• First Posted (Estimate): February 9, 2010

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: December 31, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Left ventricular dysfunction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Ventricular Dysfunction; Ventricular Dysfunction, Left; Molecular Mechanisms of Pharmacological Action; Enzyme Activators; Riociguat
• Other Study ID Numbers: 14549